Antiproteinuric Effects of Liraglutide Treatment

Diabetic Kidney Disease Clinical Trial

— LIRALBU  

Official title:

Antiproteinuric Effects of Liraglutide Treatment in Patients With Type 2 Diabetes and Albuminuria: A Randomised, Placebo-Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02545738
• Other study ID #: 2014-004502-15
• Status: Completed
• Phase: Phase 4
• First received: April 13, 2015
• Last updated: August 9, 2016
• Start date: April 2015
• Est. completion date: May 2016

Study information

• Verified date: August 2016
• Source: Steno Diabetes Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Health and Medicines Authority
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to determine the effect of Liraglutide on albuminuria in type 2 diabetes.

Description:

Initial findings point to a clinically significant antiproteinuric effect of liraglutide treatment, possibly independent from blood pressure reduction. The mechanism behind is unclear and the magnitude of albuminuria reduction needs to be verified. Antiproteinuric effects are usually renoprotective and potentially also cardioprotective and may suggest an additional benefit from liraglutide treatment.

The aim of this study is to evaluate the magnitude of the antiproteinuric effect of short-term liraglutide treatment (12 weeks) in patients with type 2 diabetes and albuminuria. In addition, possible mechanisms causing the antiproteinuric effect will be explored.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Must give written informed consent before participation. Patient information and consent form must be approved by the Danish Medicines Agency and the Regional Scientific Ethical Committee

2. Male or female patients >18 years with type 2 diabetes (WHO criteria).

3. HbA1c = 48 mmol/mol (6.5 %)

4. eGFR = 30 ml/min/1.73 m2 (estimated by MDRD formula)

5. Fertile female patients must use chemical, hormonal or mechanical contraceptives or be in menopause (i.e. must not have had regular menstrual bleeding for at least one year) or have undergone bilateral oophorectomi or have been surgically sterilized or hysterectomised at least six months prior to screening

6. Patients must be on stable RAAS-blocking treatment (unchanged dose 4 weeks before inclusion)

7. Geometic mean urine albumin-to-creatinine ratio (UACR) above 30 mg/g at screening (measured in at least two of three consecutive morning spot urine samples)

8. Systolic blood pressure (SBP) must be lower than 180 mm Hg at screening.

9. Patients must be on stable glucose lowering medication for at least two weeks before the first visit.

10. Must be able to communicate with the investigator.

Exclusion Criteria:

1. SBP > 180 mm Hg at screening

2. Type 1 diabetes mellitus

3. Chronic pancreatitis / previous acute pancreatitis

4. Known or suspected hypersensitivity to trial product(s) or related products.

5. Treatment with oral glucocorticoids, calcineurin inhibitors, dipeptidyl peptidase 4 (DPP4) inhibitors, glucagon like peptide-1 agonists and sodium-glucose co-transporter 2 (SGLT-2) inhibitors, which in the investigator's opinion could interfere with glucose or lipid metabolism 90 days prior to screening

6. Cancer (except basal cell skin cancer or squamous cell skin cancer) or any other clinically significant disorder, except for conditions associated with type 2 diabetes history, which in the investigators opinion could interfere with the results of the trial

7. Inflammatory bowel disease

8. Cardiac disease defined as: Decompensated heart failure (NYHA class III-IV) and/or diagnosis of unstable angina pectoris and/or myocardial infarction within the last 6 months

9. Previous bowel resection

10. Body mass index <18.5 kg/m2

11. Females of childbearing potential who are pregnant, breast-feeding, intending to become pregnant or not using adequate contraceptive methods

12. Clinical signs of diabetic gastroparesis

13. Impaired liver function (transaminases > two times upper reference levels)

14. The receipt of any investigational product 90 days prior to this trial

15. Known or suspected abuse of alcohol or narcotics

16. Subjects with personal or family history of medullary thyroid carcinoma or a personal history of multiple endocrine neoplasia type 2

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetic Kidney Disease
• Diabetic Nephropathies
• Kidney Diseases

Intervention

Drug:
• Liraglutide
active treatment
• placebo
placebo

Locations

Country	Name	City	State
Denmark	Peter Rossing	Gentofte

Sponsors (2)

Lead Sponsor	Collaborator
Steno Diabetes Center	Novo Nordisk A/S

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in albuminuria	24h urinary albumin excretion rate (UAER mg/24h)	24 weeks	No
Secondary	Change in renin-angiotensin system hormones	renin (activity and concentration), angiotensin 1+2, aldosteron (concentrations)	24 weeks	No
Secondary	Change in kidney function	Cr-EDTA-GFR (ml/min/1.73m2)	24 weeks	No
Secondary	Change in 24h blood pressure	24 h systolic and diastolic blood presure (mmHg)	24 weeks	No
Secondary	Change in markers of inflammation	TNF-alfa, mcp (concentration)	24 weeks	No
Secondary	24h heart rate	puls in BPM	24 weeks	No